Identification

Name
Enoximone
Accession Number
DB04880
Type
Small Molecule
Groups
Approved, Investigational
Description

Enoximone is a selective phosphodiesterase inhibitor with vasodilating and positive inotropic activity that does not cause changes in myocardial oxygen consumption. It is used in patients with congestive heart failure. Trials were halted in the U.S., but the drug is used in various countries.

Structure
Thumb
Synonyms
  • Perfan
External IDs
MDL 17,043 / MDL-17043
International/Other Brands
Perfan
Categories
UNII
C7Z4ITI7L7
CAS number
77671-31-9
Weight
Average: 248.301
Monoisotopic: 248.061948328
Chemical Formula
C12H12N2O2S
InChI Key
ZJKNESGOIKRXQY-UHFFFAOYSA-N
InChI
InChI=1S/C12H12N2O2S/c1-7-10(14-12(16)13-7)11(15)8-3-5-9(17-2)6-4-8/h3-6H,1-2H3,(H2,13,14,16)
IUPAC Name
4-methyl-5-[4-(methylsulfanyl)benzoyl]-2,3-dihydro-1H-imidazol-2-one
SMILES
CSC1=CC=C(C=C1)C(=O)C1=C(C)NC(=O)N1

Pharmacology

Indication

For the treatment of congestive heart failure.

Structured Indications
Not Available
Pharmacodynamics

Enoximone is a phosphodiesterase inhibitor (type III) that increases the force of contraction of the heart and dilates blood vessels. In June 2005, Myogen announced that they were discontinuing development of enoximone due to negative results. The drug is approved for use in the UK.

Mechanism of action

Further research is required to determine accurately the mechanism of action of drugs with phosphodiesterase inhibitory activity, however, inhibition of PDE3 inhibits degredation of cGMP. This allows for increased NO release and vascular relaxation.

TargetActionsOrganism
AcGMP-inhibited 3',5'-cyclic phosphodiesterase A
inhibitor
Human
Absorption

Bioavailabvility is 50% following oral administration.

Volume of distribution
Not Available
Protein binding

85%

Metabolism

Hepatic oxidation

Route of elimination
Not Available
Half life

4-10 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Sandroni C, Cavallaro F, Caricato A, Scapigliati A, Fenici P, Antonelli M: Enoximone in cardiac arrest caused by propranolol: two case reports. Acta Anaesthesiol Scand. 2006 Jul;50(6):759-61. [PubMed:16987374]
  2. van der Maaten JM, de Vries AJ, Rietman GW, Gallandat Huet RC, De Hert SG: Effects of preemptive enoximone on left ventricular diastolic function after valve replacement for aortic stenosis. J Cardiothorac Vasc Anesth. 2007 Jun;21(3):357-66. Epub 2006 May 4. [PubMed:17544886]
  3. Schauvliege S, Van den Eede A, Duchateau L, Gasthuys F: Cardiovascular effects of enoximone in isoflurane anaesthetized ponies. Vet Anaesth Analg. 2007 Nov;34(6):416-30. Epub 2007 Aug 13. [PubMed:17696974]
  4. Boldt J, Suttner S: Combined use of ultra-short acting beta-blocker esmolol and intravenous phosphodiesterase 3 inhibitor enoximone. Expert Opin Pharmacother. 2007 Sep;8(13):2135-47. [PubMed:17714066]
External Links
Human Metabolome Database
HMDB15599
KEGG Drug
D04004
PubChem Compound
53708
PubChem Substance
46505575
ChemSpider
48492
BindingDB
50241379
ChEBI
135010
ChEMBL
CHEMBL249856
Therapeutic Targets Database
DAP000611
PharmGKB
PA164768794
Wikipedia
Enoximone
ATC Codes
C01CE03 — Enoximone

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3TerminatedTreatmentCongestive Heart Failure (CHF)2
4Unknown StatusTreatmentMicrocirculation / Severe Sepsis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)256 dec °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.0682 mg/mLALOGPS
logP1.97ALOGPS
logP1.84ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)9.68ChemAxon
pKa (Strongest Basic)-7.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area58.2 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity70.04 m3·mol-1ChemAxon
Polarizability25.67 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9659
Blood Brain Barrier+0.77
Caco-2 permeable-0.5178
P-glycoprotein substrateNon-substrate0.6512
P-glycoprotein inhibitor INon-inhibitor0.9333
P-glycoprotein inhibitor IINon-inhibitor0.992
Renal organic cation transporterNon-inhibitor0.892
CYP450 2C9 substrateNon-substrate0.6586
CYP450 2D6 substrateNon-substrate0.7445
CYP450 3A4 substrateNon-substrate0.6998
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9431
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorInhibitor0.5842
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8173
Ames testNon AMES toxic0.7916
CarcinogenicityNon-carcinogens0.9418
BiodegradationNot ready biodegradable0.9737
Rat acute toxicity2.0807 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9554
hERG inhibition (predictor II)Non-inhibitor0.8438
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-3910100000-ff2ed6a9d4b5b2530185

Taxonomy

Description
This compound belongs to the class of organic compounds known as aryl-phenylketones. These are aromatic compounds containing a ketone substituted by one aryl group, and a phenyl group.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbonyl compounds
Direct Parent
Aryl-phenylketones
Alternative Parents
Thiophenol ethers / Benzoyl derivatives / Carbonylimidazoles / Alkylarylthioethers / Vinylogous amides / Heteroaromatic compounds / Ureas / Sulfenyl compounds / Azacyclic compounds / Organopnictogen compounds
show 3 more
Substituents
Aryl-phenylketone / Aryl thioether / Benzoyl / Thiophenol ether / Imidazole-4-carbonyl group / Alkylarylthioether / Monocyclic benzene moiety / Benzenoid / Azole / Heteroaromatic compound
show 14 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Metal ion binding
Specific Function
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes.
Gene Name
PDE3A
Uniprot ID
Q14432
Uniprot Name
cGMP-inhibited 3',5'-cyclic phosphodiesterase A
Molecular Weight
124978.06 Da
References
  1. Boldt J, Suttner S: Combined use of ultra-short acting beta-blocker esmolol and intravenous phosphodiesterase 3 inhibitor enoximone. Expert Opin Pharmacother. 2007 Sep;8(13):2135-47. [PubMed:17714066]
  2. Sandroni C, Cavallaro F, Caricato A, Scapigliati A, Fenici P, Antonelli M: Enoximone in cardiac arrest caused by propranolol: two case reports. Acta Anaesthesiol Scand. 2006 Jul;50(6):759-61. [PubMed:16987374]

Drug created on October 20, 2007 13:43 / Updated on November 09, 2017 03:48